Dioctyl sodium sulfosuccinate solutions in capsules



United States Patent DIOCTYL SODIUM SULFOSUCCINATE SOLUTIONS IN CAPSULESLyell J. Klotz, Cincinnati, Ohio, assignor to Lloyd gtl'fithers, Inc.,Cincinnati, Ohio, a corporation of No Drawing. Application May 1, 1956Serial No. 581,855

4 Claims. (Cl. 167-56) The present invention relates to means forsolubilizing dioctyl sodium sulfosuccinate in oils and resultingcompositions having utility in the treatment of constipation. The use ofdioctyl sodium sulfosuccinate in milk, fruit uices and the like fortreating constipation has been proposed heretofore. Wilson and DickinsonJ.A.M.A., vol. 158, pages 261-263 (1955). See also Vaughan applicationSerial No. 537,873, filed September 30, 1955. The use of dioctyl sodiumsulfosuccinate for the treatment of constipation has been demonstratedas safe, reliable and elfective and it is available today for thispurpose in the form of oil solutions in capsule form.

Difficulties have been encountered in preparing sufficientlyconcentrated solutions of dioctyl sodium sulfosuccinate in oil so thatcapsules of desirable size and content can be used. This has been due(1) to the tendency of the dioctyl sodium sulfosuccinate to precipitatefrom the oil solutions when present in desirable concentrations,particularly at room temperature and below and (2) to the failure ofcommonly available oils to dissolve dioctyl sodium sulfosuccinate atother desirable concentrations.

As for (1), it was found, for example, that ml. capsules containingabout 40 mg. of dioctyl sodium sulfosuccinate per capsule tend toundergo separation with precipitation of the dioctyl sodiumsulfosuccinate, when the temperature falls below room temperature.Furthermore, solutions of this or greater strength are encapsulated onlywith difficulty because of the separation of the dioctyl. sodiumsulfosuccinate,

mg. or more of dioctyl sodium sulfosuccinate per capsule could not besatisfactorily prepared as the limited amount of oil present was notsulficient to dissolve the dioctyl sodium sulfosuccinate. Thesecharacteristics posed limitations and serious problems both in theencapsulating operation and in the final preparation of pharmaceuticallyacceptable stable capsules having the desired pharmaceutical eleganceand providing the therapeutically useful dosage in convenient, practicalcapsule size.

Commercial experience in this field has demonstrated that it isdesirable, for practical purposes, to have the dioctyl sodiumsulfosuccinate in solution in the oil, and further, that the resultingsolutions should preferably be free from any tendency to separate attemperatures as low as C. In attempts to solve this problem, known aswell as some unknown possible pharmaceutically ac ceptable solubilizingagents were investigated along with various types of oils. All agentstried were either found lacking for one reason or another or weretherapeutically unacceptable until the glyceryl oleates were found to becompatible with both the oil and the dioctyl sodium sulfosuccinate, andunexpectedly discovered to be capable of solubilizing the latter in theoil. The resulting solutions were also found to be stable and, ifsufficient solubilizer is present to be free from separation atrefrigerating temperatures.

The following examples will serve to illustrate the invention.

As for (2), it wasfound, for example, that A ml. capsules containing 60EXAMPLE I Dioctyl sodium sulfosuccinate 661 lbs., 5 oz., 340

grains. Glyceryl mono-oleate 13 gal., 1 pt., 10 H. 02.,

425 minims.

Mineral oil, q.s. ad 330 gal., 2 pt., 61 minims.

(4) Add suflicient mineral oil to bring to exact volume given above. Mixwell, and filter. (5) Encapsulate into 5,000,000 ml, (4 minims) eachsoft gelatin capsules.

The capsules prepared as above contain 60 mg. of dioctyl sodiumsulfosuccinate per capsule.

EXAMPLE II This example corresponds to and is prepared in accordancewith Example I, except that 1322 lbs., 10 02.,

' 680 grains of dioctyl sodium sulfosuccinate are used in are preferred.The following table illustrates the ap-' proximate amount of materialsrequired to make ml. of solution for use in the preparation of 400capsules of this type.

Table A B O Dloeytyl Sodium Sull'osuccinate 16 24 48. Glycerylmono-oleate 0.5 0.5 2.5 Mineral Oil, q.s. to make 100 ml. 87 80 6 Thesolutions of A, B and C can be used to make M4 ml. capsules containing,respectively, 40 mg., 60 mg. and mg. of dioctyl sodium sulfosuccinate.Similarly, the solutions can be used to make /8 ml. (2 minims) capsulescontaining, respectively, 20 mg, 30 mg. and 60 mg. of dioctyl sodiumsulfosuccinate, and /2 m1. (8 minims) capsules containing 80 mg., 120mg. and 240 mg. of dioctyl sodium sulfosuccinate. For most purposes,where high concentrations are desired, capsules of around the ml. sizeand containing up to 200 mg. of dioctyl sodium sulfosuccinate with about3.54.5% by volume of glyceryl oleate are generally preferred.

The glyceryl oleates employed in the present invention are selected fromthe class of glyceryl monoand dioleates or mixtures of the same. Theyare equivalents for purposes of the present invention and the desiredsolubilizing effects can be readily obtained by use of the commerciallyavailable glyceryl monoand di-oleate preparations. These preparationsnormally contain mixtures of the monoand di-oleates along with orwithout some glyceryl tri-oleate. For example, the commercial glycerylmono-oleate is made up primarily of the mono-oleate along with somedi-oleate and the commercial glyceryl di-oleate is made up primarily ofthe til-oleate along with some mono-oleate.

The glyceryl monoor di-oleate or mixtures of the same can be present inabout 0.5 to 25% by volume of the total volume of the oil solution.Larger amounts e.g. up to 50% by volume, can be employed although theuse of more than about 4% by volume has been found not to result in anyappreciable additional beneficial elfects at ordinary concentrations ofthe type described above. Smaller amounts can also be employed, forexample, about 0.25% in m1. capsules containing 40 mg. of dioctyl sodiumsulfosuecinate, although the use of .at least about 0.5% with a range ofabout 0.5 to 5% by volume is preferred even at the lower concentrationsto prevent possible precipitation of the dioctyl sodium .sulfosuccinateat refrigerating temperatures i.e. the low temperatures (e.g. about C.)at which pharmaceutical preparations are frequently shipped and stored.The present invention is thus directed in essence to stable solutionsmade up of dioctyl sodium sulfosuccinate and glyceryl monoand/ordi-oleates in a pharmaceutical oil carrier where the ratio of oil todioctyl sodium sulfosuccinate is such that the oil per se will notdissolve the dioctyl sodium sulfosuccinate (or if in solution will notmaintain it in solution at temperatures below room temperature e.g.about 20 C. or less), and the ratio of glyceryl oleate to the totalvolume of the solution is such that the oil will dissolve the dioctylsodium sulfosuccinate and maintain it in solution at temperatures belowroom temperature.

The oils employed in the present invention are selected from thewell-known non-toxic, inert, liquid oil class used as pharmaceuticalcarriers or diluents. These include mineral oil, vegetable oils such aslinseed, corn, cottonseed, peanut and the like oils as well as animaloils such as lard oil. The preferred oil is the relatively in expensivepharmaceutical or medicinal grade of mineral oil.

The solutions of the present invention can be advantageously employed incapsule form as shown above. The solutions can also be used insuppository form, e.g. incorporated in cacao butter or like base. Thesolutions in addition can be employed as a medium or carrier for otherpharmaceutically active materials e.g. scopolamine methyl bromide, etc.

I claim:

1. A composition in dosage unit soft gelatin capsule form for treatingconstipation comprising a mineral oil solution containing 40-200 mg. ofdioctyl sodium sulfosuccinate and about 0.5 to 25 by volume based on thetotal volume of the oil solution of a member selected from the groupconsisting of glyceryl monoand dioleates, the ratio of mineral oil todioctyl sodium sulfosuccinate in said gelatin capsule being such thatthe mineral oil per se will not maintain the dioctyl sodiumsulfosuccinate in solution in the absence of said glyceryl oleate.

2. A composition in dosage unit soft gelatin capsule form for treatingconstipation comprising about /4 ml. of a mineral oil solutioncontaining about 40 mg. of dioctyl sodium sulfosuccinate and about 0.5to 5% by volume based on the total volume of the oil solution ofglyceryl mono-oleate.

3. A composition in dosage unit soft gelatin capsule form for treatingconstipation comprising about ml. of a mineral oil solution containingabout mg. of dioctyl sodium sulfosuccinate and about 0.5 to 5% by volumebased on the total volume of the oil solution of glyceryl mono-oleate.

4. A composition in dosage unit soft gelatin capsule form for treatingconstipation comprising about A ml. of a mineral oil solution containingabout mg. of dioctyl sodium sulfosuccinate and about 3.5 to 4.5% byvolume based on the total volume of the oil solution of glycerylmono-oleate.

References Cited in the file of this patent UNITED STATES PATENTS629,141 Weyland July 18, 1899 1,087,843 Smith Feb. 17, 1914 2,327,564Scherer Aug. 24, 1943 OTHER REFERENCES Aerosol Wetting Agents, Am.Cyanamid and Chem. Corp., N.Y.C. (Booklet), 1941, pp. 3, 4, 8, 1346,4548, 67-68.

Greenberg: Handbook of Cos. Materials, Intersci. Pub. Co., N.Y.C., 1954,pp. -141 and 230.

Wilson et al.: J. Amer. Med. Asso., 158:4 (May 28, 1955), pp. 261-263.

Canadian Med. Asso. Iour., October 1942, pp. 344- 349.

Spalton: Pharmaceutical Emulsions and Emulsifying Agents, The Chemistand Druggist, London, 1950, pp. 14-16.

1. A COMPOSITION IN DOSAGE UNIT SOFT GELATIN CAPSULE FORM FOR TREATINGCONSTIPATION COMPRISING A MINERAL OIL SOLUTION CONTAINING 40-200 MG. OFDIOCTYL SODUIM SULFOSUCCINATE AND ABOUT 0.5 TO 25% BY VOLUME BASED ONTHE TOTAL VOLUME OF THE OIL SOLUTION OF A MEMBER SELECTED FROM THE GROUPCONSISTING OF GLYCERYL MONO- AND DIOLEATES, THE RATIO OF MINERAL OIL TODIOCTYL SODUIM SULFO SUCCINATE IN SAID GELATIN CAPSULE BEING SUCH THATTHE MINERAL OIL PER SE WILL NOT MAINTAIN THE DIOCTYL SODIUMSULFOSUCCINATE IN SOLUTION IN THE ABSENCE OF SAID GLYCERYL OLEATE.